Sodium hydride → (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine

HRID 1814972Notes

Reaction equation

HRID 1814972 reaction equation
[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][C:13](=[O:18])[N:12]([CH3:19])[C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:22]([O:25][C@H:26]([CH3:32])[CH2:27][CH2:28][CH2:29][CH2:30]Cl)(=[O:24])[CH3:23]>CS(C)=O>[C:22]([O:25][C@H:26]([CH3:32])[CH2:27][CH2:28][CH2:29][CH2:30][N:14]1[C:15](=[O:17])[C:16]2[N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:9]=[N:10][C:11]=2[N:12]([CH3:19])[C:13]1=[O:18])(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6856307-Benzyl-3-methylxanthineHCID 110194345-(R)-Acetoxy-1-chlorohexane

Product 1

HCID 53701360(R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthineYield 84.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

To a stirring suspension of 7-benzyl-3-methylxanthine (25.6 g, 100 mmol) (which had been prepared as described for CT22404 of Example 18) in dimethylsulfoxide (200 ml) was added 95% sodium hydride (3.2 g, 133 mmol) in portions over 10 minutes. After stirring for 30 minutes, (R)-5-acetoxy-1-chlorohexane (19.63 g, 110 mmol) was added neat. After heating at 70-80° C. for 6 hours, the reaction mixture was quenched by addition of water (500 ml) and extracted with ethyl acetate (3×150 ml). The combined extracts were washed with water (150 ml), saturated aqueous sodium chloride solution (150 ml) and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave a residue which was purified by flash chromatography on silica gel eluting with 20% hexane/ethyl according to give (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine (33.7 g).

Workup

  1. customhad been prepared
  2. customthe reaction mixture was quenched by addition of water (500 ml)
  3. extractionextracted with ethyl acetate (3×150 ml)
  4. washThe combined extracts were washed with water (150 ml), saturated aqueous sodium chloride solution (150 ml)
  5. dry with materialdried over magnesium sulfate
  6. customEvaporation of the solvent under reduced pressure
  7. customgave a residue which
  8. customwas purified by flash chromatography on silica gel eluting with 20% hexane/ethyl according

Sources & evidence

ORD record
ord-af6ab71ad69243a09f4a3248277532a4
Source dataset
uspto-grants-2005_04
Patent number
US06878715B1

Reaction notes

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